摘要
背景与目的:研究表明硫氧还蛋白还原酶(thioredoxin reductase,TrxR)在肿瘤组织中的表达较正常组织中明显增多且活性升高,但关于肿瘤生长与血TrxR活性的关系报道却很少。本实验的目的是研究小鼠H22肝癌皮下移植瘤的生长与血TrxR活性的关系。方法:建立H22肝癌昆明小鼠皮下移植瘤动物模型,分为5组:空白组不接种肿瘤细胞,模型组接种肿瘤细胞,这两组小鼠均给予5‰羧甲基纤维素钠灌胃作为对照;乙烷硒啉低、中、高剂量组均接种肿瘤细胞,并分别灌胃给予36mg/kg、72mg/kg、216mg/kg乙烷硒啉。于肿瘤接种前、肿瘤生长至100mm3给药前、给药第1天、给药第4天及给药第10天5个时间点行眼眶取血,二硫代双硝基苯甲酸(dithio-bis-nitrobenzoic acid,DTNB)法测定血浆TrxR活性。处死小鼠剥离皮下肿瘤,DTNB法测定肿瘤组织TrxR活性。结果:给药结束时低、中、高剂量乙烷硒啉组小鼠的抑瘤率分别达到59.5%、74.3%、74.9%。空白组小鼠血TrxR活性稳定;接种肿瘤后小鼠血TrxR活性随肿瘤体积增大而增加,呈明显正相关;给药结束时,低、中、高剂量乙烷硒啉组小鼠血TrxR活性抑制率分别为59.2%、68.4%、68.9%,而肿瘤组织中TrxR活性抑制率分别为15.3%、25.8%、29.8%。结论:H22肝癌小鼠血TrxR活性与其肿瘤生长呈正相关;不同剂量的TrxR抑制剂乙烷硒啉干预后,血TrxR活性能够被不同程度地抑制,与肿瘤生长的抑制呈一致性。
Background and Objective: The expression and activity of thioredoxin reductase (TrxR) are significantly higher in tumor tissues than in normal tissues, but the correlation of plasma TrxR activity to tumor growth has seldom been reported. This study was to evaluate the correlation of plasma TrxR activity to the growth of hepatocellular carcinoma (HCC) H22 cell xenografts in mice. Methods: H22 cells were injected subcutaneously into Kunming mice to establish HCC model. The mice were divided into control group, mice group, low dose (36 mg/kg), moderate dose (72 mg/ kg) and high dose (216 mg/kg) ethaselen groups. The mice in control group and model group were given 5%. sodium carboxymethyl cellulose (CMC-Na). Blood samples were drawn before tumor cell inoculation, when tumor volume reached 100 mm3, and at Days 1, 4 and 10 of treatment. TrxR activity in plasma and tumor tissues was detected by dithio-bis-nitrobenzoic acid (DTNB) method. Results. The inhibition rates of tumor growth were 59.5% in low dose ethaselen group, 74.3% in moderate dose ethaselen group, and 74.9% in high dose ethaselen group. Plasma TrxR activity was stable in control mice, and was correlated positively to tumor volume in tumor-bearing mice. At the end of treatment, the inhibition rates of TrxR activity in plasma and tumor were 59.2% and 15.3% in low dose ethaselen group, 68.4% and 25.8% in moderate dose ethaselen group, 68.9% and 29.8% in high dose ethaselen group. Conclusions- Plasma TrxR activity is correlated positively to tumor growth. Ethaselen can inhibit TrxR activity corresponding to tumor growth inhibition.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2009年第5期472-477,共6页
Chinese Journal of Cancer
基金
国家自然科学基金项目(No.30472036)~~